Vaccines represent a proven and effective approach for assuring widespread protection of large populations and can be used to reduce the number of susceptible individuals prior to or immediately following a bioterrorism attack. This project addresses two significant problems that are raised by current bioterrorism threats: 1) the need for an easy method of mass vaccination and 2) the general lack of enteric disease vaccines, several of which are NIAID "category B" agents (e.g. Salmonella). In this context we propose to use Aridis' vaccine stabilization and delivery technologies to develop a room temperature stable, live, oral Salmonella typhi Ty21a vaccine in a delivery system, that requires no reconstitution or preparation time, e.g., quick dissolving thin films or tablets applied directly to the tongue. If we demonstrate that this system is compatible with delivery of Salmonella typhi and protects against typhoid fever, then this will be a significant step forward in developing stabilization and delivery systems for the other category A and B priority bacterial pathogens (approximately 40% of the total pathogens). The rationale underlying this approach is to exploit the extensive safety record of the existing live, oral Salmonella enterica serovar Typhi strain Ty21 a vaccine. Initially, we will use formulation selection and freeze dry foaming to produce solid foam preparations of Ty21a that do not require refrigeration. Next, we will develop a process to produce powders from the solid foam that do not require refrigeration and are suitable for further processing for oral delivery. Lastly, we will develop an alternative procedure, spray drying, to directly produce powders that do not require refrigeration and are suitable for further processing for oral delivery. Future goals, which will be part of a phase 2 SBIR application, will be to develop temperature responsive labels that ensure product quality at the single dose level and an easy to administer oral delivery system that does not require needles/syringes, reconstitution or skilled healthcare professionals for administration.